Bone marrow suppression is a common hematopoietic system disease seen in clinical practice, and many factors such as radiation damage caused by radiation therapy and/or chemotherapy of neoplastic diseases in various systems as well as ionizing radiation, viral hepatitis, micro virus infection or drugs and the like can result in bone marrow suppression. Bone marrow suppression is mainly represented by injuries of bone marrow microenvironment, hematopoietic stem cells, hematopoietic cell growth factors, etc, together with inhibition of cells in one system, two systems and three systems of granulocytic system, erythrocytic system, and megakaryocytic system; amongst, agranulocytosis can cause severe infections, obvious reduction of erythrocytes can cause severe anemia, and obvious decrease of platelets can cause serious hemorrhage and even lead to death. Because marrow suppression seriously threatens lives and health of patients, especially producing adverse effects on neoplastic patients receiving chemoradiation, currently, many research groups are engaged in searching for potent drugs to prevent and treat bone marrow suppression.
Ziyuglycoside II, with chemical name 3-O-α-L-arabinosyl-19α-hydroxyurs-12-en-28-oic acid (ziyuglycoside II), is an active constituent extracted from roots of Sanguisorba officinalis L. or S. officinalis L. var. longifolia (Bertol.) Yu et Li, plants of Sanguisorba genus (Rosaceae). CN101119740A has disclosed the use of ziyuglycoside II in preparation of drugs elevating erythrocytes and hemoglobin. However, solubility of ziyuglycoside II in water is low, and gastrointestina absorption rate after oral administration is low, that lead to low bioavailability of this drug taken orally and limit the application in clinical.
Polymer micelle, as a pharmaceutically acceptable carrier, can increase dissolution of insoluble drugs, and has characteristics of stable structure, good tissue permeability, long in vivo retention time, and making drugs effectively reach target point, etc, thus it is an excellent carrier for insoluble drugs. At present, a great variety of carrier materials are used for preparation of polymer micelles, and amphiphilic block copolymers are often utilized. Hydrophilic segment can be selected from polyethylene glycol, polyoxyethylene, povidone, chitosan, etc., while hydrophobic segment materials mainly include polypropylene, polystyrene, polyamino acid, polylactic acid, spermine or short chain phosphatides, etc. Choosing suitable polymer materials according to physicochemical properties of principal drug, thus preparing micelles and obtaining preparations with quality meeting requirements, and allowing that drugs can be effectively released and produce effect in organism, is one of major problems for designing polymer micelles.
Consequently, there is an urgent need for developing a ziyuglycoside II polymer micelle with better preparation quality and definite efficacy, that can be used for treatment and/or prevention of bone marrow suppression.